The ALL-1 gene is directly involved in acute leukemia in particular in infants and in patients with therapy-related disease. The ALL-1 gene alterations consist predominantly of chromosome translocations or partial tandem duplications. ALL-1 is the human homologue of Drosophila trithorax which plays an important role during Drosophila development. The experiments proposed here are intended to provide an understanding of the mechanisms by which ALL-1 gene alterations induce leukemia, as well as of the mode of action of normal ALL-1 and TRITHORAX. Investigations will include: 1) developing of a mouse model to assay leukemogenicity of the partially duplicated ALL-1. 2) assessing potential role of ALL-1 chimeric 1 fusion proteins, 3) characterization of genes which are turned on or off by ALL-1 fusion proteins, 4) identification and detailed characterization of trithorax and ALL-1 DNA response elements, 5) identification and purification of a multi-protein complexes containing ALL-1 and TRX. 6) identification of proteins which physically interact with highly conserved motifs within the ALL-1 and TRITHORAX proteins. 8) Functional and biochemical characterization of the product of the recently cloned human gene homologous to Drosophila ash1.